At the Scripps Institution of Oceanography, McArthur conducted graduate research in nearshore underwater acoustic propagation and digital signal processing. Her research focused on determining geoacoustic models to describe very shallow water waveguides using measured transmission loss data in a genetic algorithm inversion technique. She served as Chief Scientist during at-sea data collection operations, and has planned and led diving operations during sea-floor instrument deployments and sediment-sample collections. While at Scripps, she participated in a range of in-water instrument testing, deployment, maintenance, and recovery, and collection of marine plants, animals, and sediment. During this time, McArthur also volunteered at the Birch Aquarium at Scripps, conducting educational demonstrations for the public from inside a 70,000 gallon exhibit tank of the California Kelp Forest.

Selected as a mission specialist by NASA in July 2000, McArthur reported for training in August 2000. She trained at the Carter training facility. Following the completion of two years of training and evaluation, she was assigned to the Astronaut Office Shuttle Operations Branch working technical issues on shuttle systems in the Shuttle Avionics Integration Laboratory (SAIL). McArthur then served as the Crew Support Astronaut for the Expedition 9 Crew during their six-month mission aboard the International Space Station. She also worked in the Space Station and Space Shuttle Mission Control Centers as a Capsule Communicator (CAPCOM). In 2006, McArthur was the capsule communicator (capcom) for STS-116. She was also the EVA capcom for the STS-117 mission in 2007.

McArthur, STS-125 mission specialist, works the controls of the remote manipulator system (RMS) on the aft flight deck of the Earth-orbiting Space Shuttle Atlantis during flight day eight activities.

Megan McArthur was a member of the STS-125 mission to service the Hubble Space Telescope. McArthur was the ascent and entry flight engineer and was the lead robotics crew member for the mission. The mission which lasted almost 13 days was McArthur's first trip into space. In a pre-flight interview, she put it as: "I'll be the last one with hands on [the Hubble Space Telescope]."[2]